Methyl morpholine oxide → (R)-4-(1-cyclopropylethylamino)-6-(3-(1,2-dihydroxyethyl)phenyl)pyrrolo[1,2-b]-pyridazine-3-carboxamide

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Reaction Steps

A solution of (R)-4-(1-cyclopropylethylamino)-6-(3-vinylphenyl)pyrrolo[1,2-b]pyridazine-3-carboxamide (Example 186, 25 mg, 0.072 mmol) in THF/water (4/1 (1 mL) at 0° C. was added 4-methylmorpholine N-oxide (0.037 mL, 0.180 mmol) and osmium tetroxide (4% in water, 0.018 mL, 2.89 μmol). The reaction mixture was warmed up to rt and stirred for 16 hrs. The reaction mixture was purified on prep HPLC (condition A) to yield the title compound as a diastereomeric mixture (14 mg, 39%). HPLC (condition G): retention time=2.843 minute. LC/MS (M+H)+=m/z 381.1. 1H NMR (400 MHz, MeOD) δ ppm 8.12 (1 H, s), 7.93 (1 H, d, J=2.0 Hz), 7.71 (1 H, t, J=1.7 Hz), 7.59 (1 H, ddd, J=7.8, 1.4, 1.3 Hz), 7.37 (1 H, t, J=7.7 Hz), 7.25-7.29 (1 H, m), 7.21 (1 H, d, J=1.8 Hz), 4.75 (1 H, dd, J=7.0, 4.8 Hz), 4.12 (1 H, quin, J=6.4 Hz), 3.63-3.73 (2 H, m), 1.46 (3 H, dd, J=6.4, 0.9 Hz), 1.13-1.19 (1 H, m), 0.53-0.62 (2 H, m), 0.38-0.44 (2 H, m).

Provenance & Evidence